Systems and methods for widefield mapping of the retina

ABSTRACT

Systems and methods for constructing a widefield image of the retina from a plurality of retinal images. In one aspect, the disclosure concerns constructing a widefield image of the retina from a plurality of retinal images, comprising a base image and a plurality of peripheral images. These techniques enable medical observations of retinal phenomena in patients, such retinal vein occlusion, artery occlusion, retinal detachments, intraocular inflammation, ocular tumors, and the like, that were difficult to detect and impossible to quantify under prior art approaches.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Non-provisional patentapplication Ser. No. 13/042,026 filed Mar. 7, 2011 which claims priorityto U.S. Provisional Patent Application Ser. No. 61/310,836, filed Mar.5, 2010, the disclosures of which are hereby incorporated by referencein their entirety.

BACKGROUND OF THE DISCLOSED SUBJECT MATTER

1. Field of the Disclosed Subject Matter

The disclosed subject matter is in the field of the ophthalmology, moreparticularly, diagnostic retinal imaging, for example, of retinalcirculation, and concerns systems and methods for constructing awidefield image of the retina from a plurality of retinal images,comprising a base image and a plurality of peripheral images. Thetechniques disclosed herein enable medical observations of retinalphenomena in patients, such as retinal vein occlusion, artery occlusion,retinal detachments, intraocular inflammation, ocular tumors, and thelike, which were difficult to detect and impossible to quantify underprior art approaches.

2. Description of Related Art

Imaging of the retinal circulation has principally been done withfluorescein angiography in which the image is typically recorded with afundus camera or a scanning laser ophthalmoscope. With a fundus camerathe peripheral portion of an objective lens is used to focus light toilluminate the fundus and the central portion of the objective lens isused to create a real, inverted image of the fundus within the body ofthe camera. Additional optical elements are used to project the realimage onto the imaging plane. The scanning laser ophthalmoscope uses arotating mirror system to steer laser illumination across the fundus andan objective lens is used to gather the reflected light. The field ofview of commercial fundus cameras ranges from 30 to 60 degrees and fromcommercial scanning laser ophthalmoscopic systems from 10 to 30 degrees.Shifting the axis of either of these devices allows observation of moreperipheral portions of the patient's eye, but with decreasing imagequality secondary to decreasing width of the entrance pupil, vignetting,and induced astigmatism.

One approach that has been used to overcome limitations inherent inconventional lens based systems with coaxial illumination, is the use ofa widefield imaging system based on an ellipsoidal mirror. See Anderson,D C, Lucas, R A, Henderson, R. U.S. Pat. No. 5,815,242 (“Wide FieldScanning Laser Opthalmoscope [sic]”), incorporated herein by reference.The approach of Anderson, et al. is illustrated in FIG. 1 hereto.Elliptical mirrors have two conjugate focus points (FIG. 1A); extendingthis idea to three dimensions by rotating the ellipse would create anellipsoidal surface capable of focusing light rays emanating from theeye (FIG. 1B). The retina is illuminated by a laser, the spot of whichis scanned over the ellipsoidal surface to illuminate the conjugatepoint in the fundus. Using this technique, the Optos P200 Scanning LaserOphthalmoscope (Optos North America, Marlborough, Mass.) has a statedfield of view of 200 degrees.

SUMMARY OF THE DISCLOSED SUBJECT MATTER

The operation and advantages of the disclosed subject matter will be setforth in and apparent from the description that follows, and may belearned as well by practice of the disclosed subject matter.

In summary, the disclosure herein concerns systems and methods forretinal imaging, including for example imaging and mapping the retinalcirculation, the retinal periphery, and evaluating the size anddistribution of inflammatory lesions or intraocular tumors.

In one aspect, the disclosure concerns constructing a widefield image ofthe retina from a plurality of retinal images, comprising a base imageand a plurality of peripheral images.

The techniques disclosed herein enable medical observations of retinalphenomena in patients, such as retinal vein occlusion, that weredifficult to detect and impossible to quantify under prior artapproaches.

Other aspects and advantages of the invention will be apparent from theaccompanying drawings and the detailed description that follows.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of the disclosed subject matter andthe advantages thereof, reference is now made to the followingdescription taken in conjunction with the accompanying drawings, whereinlike reference numerals represent like parts, in which:

FIG. 1A schematically shows light paths in an elliptical mirror, and

FIG. 1B schematically shows how an ellipsoidal surface may be used toreflect light from an illumination source three-dimensionally to scanthe retina.

FIG. 2 schematically shows an azimuthal projection from a sphericalstructure, such as the eye, to a planar image.

FIGS. 3A, 3B, and 3C schematically show, respectively, orthographic,stereographic, and Gnomonic methods for making azimuthal projections ofa spherical structure, and FIG. 3D shows a distorted image due toshifting the axis of projection to the plane onto which the projectionis made.

FIG. 4 shows base and output images made in accordance with one aspectof the disclosure.

FIG. 5 shows a montage larger image made in accordance with one aspectof the disclosure.

FIG. 6 shows a panretinal mapping of circulation, made in accordancewith one aspect of the disclosure.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The following is a detailed description of certain embodiments of theinvention chosen to provide illustrative examples of how it maypreferably be implemented. The scope of the invention is not limited tothe specific embodiments described in the following detaileddescription, nor is it limited by any specific implementation,embodiment or characterization depicted in the accompanying drawings orstated or described in the invention summary or the abstract. Inaddition, nothing contained in this written description should beunderstood to imply any necessary order of steps where processes areclaimed, except as may be specified by express claim language.

Images made of the inner surface of the eye, which is nearly spherical,cannot be mapped to a flat surface without distortion as per Gauss.Although flat maps have numerous advantages over a globe, includingbeing able to be represented on a computer monitor, it is not possibleto create a flat map without inducing distortions; some attributes suchas conformality, distance, direction, scale, or area may be preserved,but not all of them can be retained simultaneously. A fundus drawingcreates a flat surface in which the radial distances of the drawing areproportional to the arc distance from the posterior pole. This producesan azimuthal projection (FIG. 2), in which distances and directions fromthe fovea, the center point of the eye, are retained. With furthereccentricity from the center there are larger distortions of the sizeand shape of structures. There are a number of possible ways to makeazimuthal projections (FIG. 3A (Orthographic), 3B (Stereographic), 3C(Gnomonic)). For nearly all of these techniques only a hemisphere isimaged, but for the retina it is common to continue anterior to theequator.

Although any one instrument cannot image the entire retina, it ispossible to direct the gaze of the patient in cardinal direction toobtain images from additional areas of the eye. Component images showvarying amounts of distortion and are not readily merged into onecomposite image. These images are not standardized to any particularaxis of the eye and the projection plane is not rigorously defined. Ifthe axis of the projection is shifted or the plane onto which theprojection is made is shifted, the resultant projection inducesadditional distortions to the projected image (FIG. 3D). In clinicalpractice widefield imaging of the eye does not have fixed, precise,relationship with the imaging system, and varying deformations can beinduced. Therefore, there can be a varying amount of image deformationin photographs taken of the eye, particularly in photographs of the moreperipheral portions of the retina. This limits the potential foraccurate measurements of sizes and areas of ocular structures andabnormalities.

Widefield imaging systems show obvious distortions because the largerfield of view makes the image deformations more readily evident. Imagestaken with a fundus camera or conventional scanning laser ophthalmoscopehave the same underlying problem, but the amount of image deformation ineach picture is less evident because of the corresponding field of viewis smaller. However, to obtain a widefield image using photographs froma fundus camera or scanning laser ophthalmoscope, a large number ofimages would have to be montaged.

In a manner similar to that used for generating fundus drawings, itshould be possible to extend the azimuthal projection from the posteriorof the eye by including the regions anterior to the equator of the eye.In such an approach, a widefield image is made, centered on theposterior portion of the eye. This image, for purposes of explanation,will be referred to as the base image. The images taken from thecardinal directions of the eye (the target images) may then beregistered to the base image (FIG. 4). In one implementation, theregistration would involve warping the peripheral images to match thedistortion characteristics of the base image. In a further aspect ofsuch an implementation, elastic image registration is performed, usingcontrol points selected in the base image and the target image. This canbe a semi-automatic operation, or, when starting with widefield imagesmay involve human intervention, because of the potential for largeamounts of image distortion.

In FIG. 4 the upper left (401) represents a raw image acquired with awidefield imaging system. The upper portion of the base image is shownin the lower left (402). The control points (411-414 and 421-424) areshown in red. Using elastic warping of the upper image, it is made tomatch with the base image, producing the output in the upper right(403).

In one implementation, an image centered on the posterior portion of theeye, and a plurality of peripheral images, are taken. Preferably, theseimages should be sharp and without systemic distortion. Image artifactsfrom the lids, lashes and nose are removed from the images. The imagesare padded at their borders with additional black pixels.

The peripheral images (401) were transformed using elastic deformationso that the posterior portions of the peripheral images matched thebase, reference image (402). Manual selection of control points (411-414and 421-424) were used in each image pair and in each case theperipheral image was warped to fit the reference base image using atransformation, such as one employing thin-plate splines. These imagesare then montaged to form a larger image (FIG. 5).

Although this image has varying distortions of the peripheral imagesreduced and matched to the posterior base image, there are stillopportunities for the merged image to deviate from actual linearcorrespondence to the retina itself.

To address the latter concern, inspection of the widefield color imagesand widefield fluorescein angiographic images was done to be able toidentify the vortex vein ampullae, which are located at the ocularequator. These locations were plotted onto the montage (widefield)fluorescein angiograms. A generalized schematic generated from reportedanatomic dimensions of the retina was created to be able to calculatethe sizes of regions within the retinal image. The montage retinalphotographs are then warped to fit the retinal drawing schematic usingthe known landmarks of the optic nerve, macula, and equator.

The reported sizes of the eye and distances between landmarks varyconsiderably. See Duke-Elder S. and Wybar K. C., The Anatomy of theVisual System, In: Duke-Elder, ed. System of Ophthalmology, Volume II.St. Louis: Mosby 1961, 220-271; Straatsma B. R., Landers M. B., KreigerA. E., Apt L., Topography of the adult human retina, UCLA Forum Med Sci.1969, 8:379-410; N. Drasdo and C. W. Fowler, Non-linear projection ofthe retinal image in a wide-angle schematic eye, Br. J. Ophthalmol.1974, 58:709-714; Taylor E., Jennings A., Calculation of total retinalarea, Br. J. Ophthalmol. 1971, 55:262-5, each incorporated herein byreference. A simplified schematic eye model based on these referenceswas developed using the following parameters: radius to retina, 11.1 mm,extension of the retina anterior to the equator: 5 mm. From thisschematic anatomical model the calculated retinal surface area of themodel was 1108 mm.sup.2, minus approximately 2 mm.sup.2 for the actualsize of the optic disc yields 1106 mm.sup.2. This value is in fairlyclose agreement with the calculated surface area of 1065 mm.sup.2 byDrasdo and Fowler and 1132 mm.sup.2 by Taylor and Jennings The actualretinal surface area corresponds to the retinal drawing azimuthal areaof 1590 mm.sup.2, reflecting the increasing distortion of retinaldrawings as compared with the actual retinal surface area. (Of coursethe retinal drawing is made much larger because it is scaled.)

Over this schematic, ocular landmarks are plotted, including the opticnerve, macula, and equator. The montage angiogram with the knownlandmarks was then warped to fit the schematic. This created aprojection of the retina to a topography similar to that used forretinal drawings that is therefore standardized from one patient to thenext. As expected this projection stretches the periphery of the eyemore than more posteriorly located areas. To measure areas of the mappedprojection one of two main approaches can be taken. A software routinecan make a transformation of the azimuthal projection image such thateach pixel of the image corresponded to the same amount of retinalsurface area. This, in effect, creates the equivalent of a Lambertazimuthal equal area projection from which areas of the retina aredirectly proportional to the number of pixels in the image of theretina. From the Lambert azimuthal equal area projection nonperfusedareas of the retina can be measured. A second related approach is to usea software routine employing an algorithm that automatically applies acorrection factor converting the area occupied by a pixel in the imageto the actual corresponding area of the retina as a function of theradial distance from the center. This second approach is somewhat morecomputationally intensive, but allows the operator to use images withthe familiar representation as they would appear on a retinal drawingform.

This imaging technique would provide very wide field images of theocular fundus, allow assessment of the retinal circulation over its fullextent, and give the opportunity for image measurement in regions notvisible by other means. For example, a condition known as centralretinal vein occlusion was thought to be due to an occlusion of thecentral retinal vein of the retina. By employing the methodologiesexplained above, a panretinal mapping of the circulation is revealed inFIG. 6.

This figure shows an image of the retina in which the entire extent ofthe retinal circulation is visible. The dark gray area surrounding theouter border of the vessels is actually where the circulation shouldalso cover. Using this methodology, it was discovered that patients withcentral retinal vein occlusion also develop large areas of vascularocclusion in the more peripheral portions of their retinas. This newfinding would have been difficult to detect and impossible to quantifywithout the image registration and measurement strategy describedherein.

While the example discussed above concerned mapping retinal circulation,the methods disclosed herein can equally well be applied to assessingother medical conditions of the retina, such as artery occlusion,retinal detachments, and the size and distribution of inflammatorylesions or intraocular tumors.

It is apparent, therefore, that the disclosed subject matter improvesover the prior art with regard to retinal imaging. Although the presentdisclosed subject matter has been described in detail, it should beunderstood that various changes, substitutions, and alterations may bereadily ascertainable by those skilled in the art and may be made hereinwithout departing from the spirit and scope of the present disclosedsubject matter as defined by the claims. The foregoing description ofspecific embodiments of the disclosed subject matter has been presentedfor purposes of illustration and description. It is not intended to beexhaustive or to limit the disclosed subject matter to those embodimentsdisclosed. Thus, it is intended that the disclosed subject matterincludes modifications and variations that are within the scope of theappended claims and their equivalents.

I claim:
 1. A method for creating a widefield image of a retina in aneye, the retina being substantially spherical and internally having aposterior area and a plurality of peripheral areas, the peripheral areaseach having a posterior portion disposed proximate the posterior area,comprising: taking a photographic base image of the posterior area;taking a photographic peripheral image of the peripheral areas;transforming the peripheral images using elastic deformation so that theposterior portions of the peripheral images substantially match thecorresponding portions of the base image; warping each peripheral imageto fit the base image; and montaging the warped peripheral images withthe base image to form the widefield retinal image.
 2. The method ofclaim 1, further comprising selecting common control points in eachperipheral image and the base image.
 3. The method of claim 2, whereinthe selection of common control points is performed semi-automatically.4. The method of claim 2, wherein the selection of common control pointsis performed manually.
 5. The method of claim 2, further comprisingsuperimposing the respective control points in the base and peripheralimages.
 6. The method of claim 1, wherein at least one peripheral imageis warped using a transformation.
 7. The method of claim 6, wherein thetransformation employs thin-plate splines.
 8. The method of claim 1,further comprising taking a plurality of photographic base images of theposterior area and selecting the base image with the best sharpness andlack of systemic distortion across the image.
 9. The method of claim 1,further comprising taking a further plurality of photographic peripheralimages, and selecting the peripheral images with the best sharpness andlack of systemic distortion across the image.
 10. The method of claim 1,further comprising editing the posterior image and peripheral images toremove image artifacts from the lids, lashes and nose.
 11. The method ofclaim 1, further comprising padding the posterior and peripheral imagesat their borders with additional black pixels.
 12. The method of claim1, further comprising inspecting the base and peripheral images toidentify vortex vein ampullae; plotting the locations of the vortex veinampullae onto the montaged widefield retinal image; providing a retinalschematic based on observed anatomic dimensions of the retina; plottingocular landmarks, including the optic nerve, macula and equator onto theschematic warping of the montage image to fit the schematic using saidlandmarks.
 13. The method of claim 12, further comprising transformingthe warped montage image such that each pixel of the image correspondsto the same amount of retinal surface area.
 14. The method of claim 12,further comprising applying a correction factor to calculate the arearepresented by a pixel in the montage image to the actual correspondingarea of the retina as a function of radial distance from the center. 15.A widefield retinal image recorded on a tangible medium which has beencreated by the method of claim
 1. 16. A method of diagnostic examinationof a retina comprising examining a widefield retinal image in accordancewith claim
 15. 17. The method of claim 16, wherein said examination isan examination of circulatory and structural features visible from saidwidefield retinal image.